UCP1 gene encodes mitochondrial brown fat uncoupling protein 1, an inner mitochondrial membrane protein essential for thermogenic respiration in brown and beige adipocytes. Based on mouse studies, UCP1 gene is directly transcriptionally regulated by EBF2 transcription factor which binds to regulatory elements of the UCP1 gene to activate UCP1 gene transcription (Rajakumari et al. 2013; Wang et al. 2014; Shao et al. 2014; Shao et al. 2021). EBF2 facilitates recruitment of the PPARG:RXRA transcription factor complex to the PPAREs (peroxisome proliferator activator response elements) in the vicinity of EBF binding sites at the UCP1 gene locus. PPARG augments UCP1 gene transcription synergistically with EBF2 (mouse studies: Rajakumari et al. 2013; Shao et al. 2021). EBF2-mediated recruitment of the BAF complex to regulatory sequences in the UCP1 gene locus may precede EBF2-facilitated binding of PPARG to the UCP1 gene locus (mouse study Shao et al. 2021). During differentiation of beige adipocytes in mouse inguinal white adipose tissue Ebf2 and Pparg synergistically upregulate Ucp1 mRNA levels (Stine et al. 2016). In mouse, depletion of DPF3, a subunit of the BAF chromatin remodeling complex that binds EBF2 and promotes transcription of EBF2 target genes, leads to downregulation of UCP1 mRNA (Shapira et al. 2017). Blnc1 lncRNA, a cofactor of EBF2, significantly increases binding of EBF2 to the UCP1 gene locus and EBF2-mediated transcriptional activation of UCP1 (mouse study Zhao et al. 2014; mouse and human study Mi et al. 2017). MLL4 histone methyltransferase complex is required for the formation of the super-enhancer at the UCP1 gene locus (mouse study Lai et al. 2017). UCP1 gene expression is negatively regulated by ZNF423-mediated inhibition of EBF2 transcriptional activity, which is associated with the recruitment of the NuRD complex to the UCP1 gene regulatory sequences (mouse study Shao et al. 2021).